In many areas of the natural sciences and technology, it is necessary to reliably and rapidly detect in a liquid and/or gaseous sample one or more analytes in a qualitative and/or quantitative manner. For example, as part of preventive diabetes care and/or diabetes treatment, it is generally necessary to determine blood sugar level at least once a day, generally multiple times, to guide individuals having diabetes to take appropriate countermeasures if deviations from a normal value or range occur.
So that the daily routine of such individuals is not compromised any more than is necessary, devices and methods have been developed that allow blood sugar measurements not only in a clinical environment but also in the workplace or home, as well as during leisure activities. Such devices and methods generally are based on using one or more disposable test elements, which are known and available in different forms. For example, test elements can be in the form of test strips, test tapes, test disks, test needles or in other forms.
Test elements often include one or more test fields having at least one analyte-specific detection reagent as part of the test chemistry. The detection reagent is selected and designed for carrying out a detectable reaction in the presence of the analyte of interest. Examples of commercially available test elements include, but are not limited to, Accu-Chek® Aviva, Accu-Chek® Performa, Accu-Chek® Active, Accu-Chek® Go or Accu-Chek® Mobile test cassette with appropriate test instruments such as Accu-Chek® Aviva, Active, Go and Mobile from Roche Diagnostics Operations, Inc. (Indianapolis, Ind.)
Intl Patent Application Publication No. WO 2010/052306 describes a diagnostic test element for detecting an analyte of interest in a body fluid sample. The test element includes a test field having a detection reagent configured to undergo a detectable optical change in the presence of the analyte. The test field has at least one detection layer that includes the detection reagent and that has particles with at least 90% of all the particles of the detection layer having an actual particle size of less than 10 μm.
Likewise, Int'l Patent Application Publication No. WO 2010/052307 describes a test element for detecting an analyte of interest in a sample. The test element includes at least one test field having a test field surface and having a detection reagent configured to carry out a detectable reaction in the presence of the analyte. In addition, the test element has at least one distribution element having at least one distribution surface facing the test field surface with at least one capillary gap being formed between the distribution surface and the test field surface. In test elements, it is possible to use one or more different test chemistries, such as an enzyme system, to convert and detect the analyte.
To provide a user with a manageable form of the enzyme system, the enzyme system can be introduced or immobilized on the test element in a dry and solid layer(s) as at least part of the test chemistry together with further reactive substances such as a mediator. The user only has to apply the sample to the layer to obtain a measurement result shortly thereafter. As such, after the sample is applied to the layer of the test element, the analyte-specific detection reaction proceeds both in the layer and completely or partly in the sample. For example, one or more reactive substances in the form of the detection reagent or constituents thereof can dissolve in the sample and can be observed up to an end point of the reaction.
These methods also can involve diffusion processes, in which the sample transports the analyte to the reactive substances and/or the detection substance formed diffuses into or out of a detection layer. For example, the end point of the reaction can be determined in electrochemical or optical systems. In this manner, the rate of formation of a detection substance can be equal to the rate of diffusion of the detection substance formed. Alternatively, a measurement signal, from which the analyte concentration can be derived, is determined at a particular time after applying the sample to the test field.
Such diffusion processes, as well as enzyme-catalyzed reactions, may be temperature-dependent. In addition, further constituents of the sample, such as cellular and/or particulate constituents (e.g., red blood cells) may have an influence on the diffusion and dissolution processes in the test element. The result can be a heavy dependence of the measured analyte concentration on the ambient temperature at which the measurement is carried out, as well as on the hematocrit (Hct) of the sample applied to the test element. Thus, in principle, there might be the risk of analyte concentration being influenced, and this in turn can lead to a challenge when dosing medicaments such as insulin. Especially in low concentration ranges of analytes, such as blood glucose in the case of a diabetic, an incorrectly high measured blood glucose can lead to too much insulin being administered. Therefore, it is important to correct the temperature-dependence and/or Hct-dependence of the particular test element system.
For example, temperature can be measured by a sensor accommodated in the measurement instrument and used to correct analyte concentration. However, this can in turn lead to faulty corrections, since temperature generally is not measured at the actual position of the chemical reaction of the analyte. Consequently, the temperature used for correction can differ from the temperature of the reaction site of the analyte, and so the correction can in turn lead to errors.
Furthermore, it is difficult to carry out a Hct correction, especially in optical systems since there are generally no purely Hct-dependent measurement values that could be used to correct analyte concentration. With electrochemical systems, however, correcting the measurement signal with regard to Hct is possible but is very laborious owing to a complex pulse sequence method and is additionally superimposed by other interfering signals in the sample.
In this manner, U.S. Pat. No. 4,250,257 describes methods and devices for analyzing whole blood samples. The methods and devices use a gel in which an inert substance is accommodated and diffuses out of the gel into the whole blood sample, whereas plasma of the whole blood sample diffuses into the gel. The diffusion of the inert substance out of the gel is inversely proportional to the Hct of the blood sample. In addition, various possibilities of bringing about a Hct correction are disclosed. In one example, a separate gel can be used to determine Hct, and from this a correction factor subsequently can be used for another blood sample. Alternatively, an analyte detection reaction and a Hct correction can be carried out by means of two different color changes, with a first color change resulting from the analyte detection reaction and with a second color change resulting from diffusion of a dye as inert medium into the sample. Furthermore, a Hct correction using albumin is described with bromocresol green (BCG).
Additionally, U.S. Pat. No. 7,548,773 describes a method of calibrating a measurement system based upon dissolution of an analyte in a reference channel. Owing to the dissolution of a known amount of analyte by sample in the reference channel, it is possible to carry out, in parallel to the actual analyte concentration determination, a differential determination relating to the reference channel to determine the reaction rate of the sample. As a result, corrections can be made on the analyte concentration. However, a disadvantage of this method is the need for dissolving a reference molecule to be determined on a capillary wall. The method also can be influenced by properties of the system that are not associated with the sample. Furthermore, the dissolution and movement of the analyte-identical calibrator is dependent on the analyte concentration. It is not possible to distinguish between influences of analyte concentration and other factors on the movement of the calibrator, and this can in turn lead to falsification of the determined analyte concentration.
For the foregoing reasons, there is a need for additional methods, devices and test elements that correct or compensate for temperature-dependence and/or Hct-dependence of a test element system when determining an analyte concentration.